Could fluvoxamine keep COVID-19 patients out of hospitals and intensive care units?

Marčec, Robert; Likić, Robert

doi:10.3325/cmj.2021.62.95

Cited by 11 publications

(11 citation statements)

References 32 publications

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“…Fluvoxamine's mechanism of action in COVID‐19 is still unknown, but it is presumed to be multifactorial (see Figure 1 ). 15 , 16 , 17 Besides being an SSRI, fluvoxamine also has high affinity for the sigma‐1 receptor (S1R) which has been shown to mediate fluvoxamine's anti‐inflammatory and immunomodulatory effects in an animal model of lipopolysaccharide (LPS) induced sepsis. 18 The same study also reported that fluvoxamine significantly reduced the production of interleukin (IL)‐6, IL‐1 beta, IL‐12 and IL‐8 induced by LPS in human heparinised peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Čalušić

Marčec

Luksa

et al. 2021

Brit J Clinical Pharma

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Aims Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) and sigma‐1 receptor agonist, has so far shown promise in the prevention of COVID‐19 progression as an early treatment option in three trials. The aim of this study was to evaluate the safety and efficacy of fluvoxamine in COVID‐19 patients if administered later in the course of the disease. Methods The study was designed as an open‐label, prospective cohort trial with matched controls. In April and May 2021, 51 ICU COVID‐19 patients hospitalised in the University Hospital Dubrava and University Hospital Centre Zagreb, Croatia, were treated with fluvoxamine 100 mg three times daily for 15 days in addition to standard therapy and they were prospectively matched for age, gender, vaccination against COVID‐19, disease severity and comorbidities with 51 ICU controls. Results No statistically significant differences between groups were observed regarding the number of days on ventilator support, duration of ICU or total hospital stay. However, overall mortality was lower in the fluvoxamine group, 58.8% ( n = 30/51), than in the control group, 76.5% ( n = 39/51), HR 0.58, 95% CI (0.36–0.94, P = .027). Conclusion Fluvoxamine treatment in addition to the standard therapy in hospitalised ICU COVID‐19 patients could have a positive impact on patient survival. Further studies on the effects of fluvoxamine in COVID‐19 patients are urgently required.

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Section: Introductionmentioning

confidence: 99%

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Čalušić

Marčec

Luksa

et al. 2021

Brit J Clinical Pharma

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“…While there is a paucity of literature examining fluoxetine's effect on the expression or activity of cyclooxygenase enzymes, other SSRIs have been shown to alter the expression and activity of these rate‐limiting enzymes. For example, the SSRI vortioxetine has been shown to inhibit the activity of both PTGS1 and PTGS2, while fluvoxamine significantly decreased the expression of PTGS2 (Marčec & Likić, 2021; Naji Esfahani et al, 2019; Talmon et al, 2020). Notably, The SSRI fluoxetine has been shown to increase the protein expression of PTGS1 and PTGS2, elevate the cerebrospinal fluid concentration of 15d‐PGJ 2 , and increase secretion of 15d‐PGJ 2 from raphe serotonergic neurons (Launay et al, 2011; Salem Sokar et al, 2016; Simplicio et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Fluoxetine‐induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15‐deoxy‐Δ^12,14PGJ₂

Ayyash

Holloway

2021

J of Applied Toxicology

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Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as nonalcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ 12,14 PGJ 2 a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ 12,14 PGJ 2 production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ 2 and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.15-deoxy-Δ 12,14 PGJ 2 (15d-PGJ 2 ), fatty acid uptake, fluoxetine, non-alcoholic fatty liver disease (NAFLD), peroxisome proliferator-activated receptor gamma (PPARG), prostaglandin, prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin-endoperoxide synthase 2 (PTGS2), selective serotonin reuptake inhibitor (SSRI), steatosis 1 | INTRODUCTION Major depressive disorder (MDD) is a prevalent and often recurrent illness affecting nearly 350 million individuals worldwide and is predicted to be the leading cause of disability by 2030 (Longfei et al., 2015; World Health Organization, 2017). A global burden of disease study saw a 49.86% increase in incident cases of depression worldwide from 1990 to 2017 (Liu et al., 2020), with the financial burden of MDD in 2010 exceeding USD 210.5 billion in the

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“…This approach is supported by a clinical trial showing reduced risk of progression to severe COVID-19 in adults treated with fluvoxamine, a high-affinity Sig-1R agonist. 10 In contrast, haloperidol, a potent Sig-1R antagonist, failed to provide clinical benefit in COVID-19 patients. 10 Furthermore, Sig-1R knockout models are associated with increased mortality in sepsis, whereas fluvoxamine improved survival in lipopolysaccharide-treated mice.…”

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confidence: 99%

“… 10 In contrast, haloperidol, a potent Sig-1R antagonist, failed to provide clinical benefit in COVID-19 patients. 10 Furthermore, Sig-1R knockout models are associated with increased mortality in sepsis, whereas fluvoxamine improved survival in lipopolysaccharide-treated mice. 11 Fluoxetine, another potent Sig-1R agonist, has been shown to inhibit SARS-CoV-2 replication, albeit by alternate mechanisms.…”

mentioning

confidence: 99%

Anaesthesia drugs, SARS-CoV-2, and the sigma-1 receptor: a complex affair. Comment on Br J Anaesth 2021; 127: e32–4

Jain¹,

Lamperti²,

Doyle

et al. 2021

British Journal of Anaesthesia

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Could fluvoxamine keep COVID-19 patients out of hospitals and intensive care units?

Cited by 11 publications

References 32 publications

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Fluoxetine‐induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15‐deoxy‐Δ^12,14PGJ₂

Anaesthesia drugs, SARS-CoV-2, and the sigma-1 receptor: a complex affair. Comment on Br J Anaesth 2021; 127: e32–4

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Could fluvoxamine keep COVID-19 patients out of hospitals and intensive care units?

Cited by 11 publications

References 32 publications

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

Fluoxetine‐induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15‐deoxy‐Δ12,14PGJ2

Anaesthesia drugs, SARS-CoV-2, and the sigma-1 receptor: a complex affair. Comment on Br J Anaesth 2021; 127: e32–4

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Fluoxetine‐induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15‐deoxy‐Δ^12,14PGJ₂